Cardiovascular disease is a leading cause of morbidity and mortality within the human population. This is particularly so in the United States and in Western European countries. Numerous causative factors have been implicated in the development of cardiovascular disease. Several of these factors include hereditary predisposition to the disease, lifestyle factors such as smoking and diet, age, gender, hypertension, and hyperlipidemia, including hypercholesterolemia. A number of these factors, particularly hyperlipidemia and hypercholesteremia, contribute to the development of atherosclerosis, a primary cause of cardiovascular disease.
High blood cholesterol concentration is one of the major risk factors for cardiovascular disease in humans. Elevated low density lipoprotein cholesterol (“LDL”) and total cholesterol are directly related to an increased risk of coronary heart disease. (Anderson et al., 1987). Although high levels of total cholesterol and LDL are risk factors in developing atherosclerosis and vascular diseases, a deficiency of high density lipoprotein cholesterol (“HDL”) has recently been recognized as an additional risk factor for developing these conditions. Several clinical trials support the theory of a protective role of HDL against atherosclerosis. One such study has demonstrated that, in women, every 1-mg/dl increase in HDL in the blood decreases the risk for coronary vascular disease by 3%. (Gordon et al., 1989).
Studies have indicated that dietary changes can reduce cholesterol in humans. Of these, particular studies have indicated that the quality, as well as the quantity, of protein ingested greatly affects serum cholesterol levels. (Carol and Hamilton, 1975; Nagaoka et al., 1992; Potter, 1995). Ingestion of vegetable protein materials in place of animal protein in the diet is associated with a lower risk of cardiovascular disease, which may reflect decreases in serum cholesterol levels. Particularly, soy protein, a vegetable protein, has been shown to reduce serum cholesterol levels relative to the animal protein casein (Nagaoka et al., 1999). A more recent meta-analysis of the effects of soy protein intake on serum lipids in humans has shown that dietary soy protein is significantly related to lowering serum concentrations of total cholesterol and LDL in humans without significantly affecting HDL-holesterol concentrations (Anderson et al., 1995).
One of the agents responsible for the ability of soy protein to lower cholesterol is the high molecular weight fraction (HMF). The HMF constitutes the non-digestible portion of soy protein that remains intact after proteolytic digestion. This fraction, therefore, is composed of a number of different peptides or peptide fragments. The HMF of soy protein, in fact, has been shown to significantly reduce serum cholesterol in both animal and human studies. It is believed that the non-digestible HMF prevents the uptake of cholesterol either by the prevention of passive uptake of cholesterol by the brush border membrane or by the prevention of protein-mediated uptake of cholesterol. In contrast, the lower molecular weight fraction, a digestible fraction of soy protein, has actually been shown to increase serum cholesterol (Sugano, et al., 1988).
Despite the potential therapeutic value of soy protein, and in particular the HMF, as a cholesterol lowering agent, the specific constituents responsible for its non-digestive and hypocholesterolemic activity have not been determined. A need, therefore, remains to identify these active constituents in an effort to provide a therapeutic agent that is more potent in reducing cholesterol and other risk factors associated with cardiovascular disease.